A study published in the Archives of Dermatological Research directly compared the efficacy of second-generation antihistamines, and the associated psychomotor function impairment. This a double-blinded, placebo controlled, crossover study concurrently compared the clinical effectiveness of promethazine – a first-generation antihistamine, and fexofenadine and olopatadine – second-generation antihistamines, by measuring their potency as peripheral inhibitors of histamine-induced wheal and flare; as well as investigated their sedative effects on the central nervous systems (CNS) using an array of psychomotor tests. The findings showed that when single therapeutic doses of fexofenadine (60 mg), olopatadine (5 mg), and promethazine (25 mg) were administered to 24 healthy volunteers, all antihistamines produced a significant reduction in the wheal and flare responses induced by histamine. However, promethazine significantly impaired psychomotor function. Whereas, fexofenadine and olopatadine had no significant effect in any of the psychomotor tests. Furthermore, promethazine, fexofenadine and olopatadine did not affect behavioral activity. Therefore, it was inferred that fexofenadine did not cause cognitive or psychomotor impairment, characteristic to first-generation antihistamines.